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A Study of Venetoclax in Combination With Cobimetinib and Venetoclax in Combination With Idasanutlin in Patients With Relapsed or Refractory Acute Myeloid Leukemia Who Are Not Eligible for Cytotoxic Therapy

Trial Status: Active

The primary objective for this study is to assess the safety and tolerability as well as preliminary efficacy of venetoclax in combination with cobimetinib, and venetoclax in combination with idasanutlin in patients with relapsed or refractory acute myeloid leukemia (R / R) AML who are not eligible for cytotoxic therapy.

Inclusion Criteria

  • Histological confirmation of relapsed or refractory AML after prior anti-leukemic therapy by WHO classification
  • Ineligible for cytotoxic therapy defined by the following: a. Age (>/=) 75 years or b. age 18- 74 years with at least one of the following comorbidities: i. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 or 3 ii. Cardiac history of congestive heart failure requiring treatment or ejection fraction (</=) 50% or chronic stable angina iii. Diffusing capacity of the lungs for carbon monoxide (</=) 65% or forced expiratory volume in the first second of expiration (</=) 65% iv. Creatinine clearance (>/=) 30 mL/min to< 45 mL/min v. any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Medical Monitor before screening and study enrollment.
  • Life expectancy of at least 12 weeks
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
  • Adequate liver and renal function

Exclusion Criteria

  • Patients with acute promyelocytic leukemia (French-American-British [FAB] class M3 AML)
  • Known active central nervous system (CNS) involvement with AML at study entry
  • ECOG Performance Status (>/=) 3 in patients who are (>/=) 75 years old or ECOG Performance Status of 4, regardless of age
  • Prior exposure to Bcl-2 inhibitors, murine double minute 2 (MDM2) antagonists or prior exposure to experimental treatment targeting Raf, mitogen-activated protein kinase (MEK), or the mitogen-activated protein kinase (MAPK) RAS/RAF/MEK/ERK MAPK pathway
  • Positive for hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) and known history of HIV, malignancy, active infection and cardiovascular diseases (CVs)
  • Received strong cytochrome (CYP) 3A inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers and moderate CYP3A inducers within 7 days prior to initiation of study treatment
  • History of symptomatic Clostridium difficile infection within 1 month prior to dosing Additional arm specific exclusion criteria: Dose Escalation Arm A (Venetoclax and Cobimetinib):
  • History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
  • Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower Arm B (Venetoclax and Idasanutlin):
  • Received the following within 7 days prior to the initiation of study treatment: Strong CYP2C8 inhibitors or CYP2C8 substrates, OATP1B1/3 substrates
  • Received the following within 14 days prior to the initiation of study treatment: Strong CYP2C8 inducers
  • History of liver cirrhosis by radiologic, clinical or laboratory data, or biopsy despite normal liver function tests
  • Received treatment with oral or parenteral anticoagulants/anti-platelet agents within 7 days prior to initiation of study treatment.

California

Los Angeles
USC / Norris Comprehensive Cancer Center
Status: ACTIVE
Sacramento
University of California Davis Comprehensive Cancer Center
Status: ACTIVE
San Francisco
UCSF Medical Center-Mount Zion
Status: ADMINISTRATIVELY_COMPLETE

Colorado

Aurora
University of Colorado Hospital
Status: COMPLETED

Massachusetts

Boston
Brigham and Women's Hospital
Status: ACTIVE
Dana-Farber Cancer Institute
Status: ACTIVE

North Carolina

Winston-Salem
Wake Forest University Health Sciences
Status: ACTIVE

Texas

Houston
M D Anderson Cancer Center
Status: ACTIVE

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Hoffmann-La Roche

  • Primary ID GH29914
  • Secondary IDs NCI-2016-00260, 2015-003386-28
  • Clinicaltrials.gov ID NCT02670044